Copper Isotopes and Copper to Zinc Ratio as Possible Biomarkers for Thyroid Cancer

Abstract

Thyroid cancer is the most common endocrine cancer. There is no systematic screening for such cancer, and the current challenge is to find potential biomarkers to facilitate an early diagnosis. Copper (Cu) and zinc (Zn) are essential micronutrients involved in the proper functioning of the thyroid gland, and changes in their concentrations have been observed in the development of cancer. Previous studies have highlighted the potential 65Cu/63Cu ratio (δ65Cu) to be a cancer biomarker. This study tests its sensitivity on plasma samples (n = 46) of Algerian patients with papillary thyroid carcinoma and a set of corresponding biopsies (n = 11). The δ65Cu ratio in blood and tumor samples was determined using multi collector inductively coupled plasma-mass spectrometry (MC-ICP-MS), and their corresponding Cu and Zn plasma total concentrations using total reflection X-ray fluorescence (TXRF). Plasma concentrations of Cu were significantly higher (1346.1 ± 328.3 vs. 1060.5 ± 216.1 μg/L, p < 0.0001), and Zn significantly lower (942.1 ± 205.2 vs. 1027.9 ± 151.4 μg/L, p < 0.05) in thyroid cancer patients as compared to healthy controls (n = 50). Accordingly, the Cu/Zn ratio was significantly different between patients and controls (1.5 ± 0.4 vs. 1.0 ± 0.3, p < 0.0001). Furthermore, the δ65Cu plasma levels of patients were significantly lower than healthy controls (p < 0.0001), whereas thyroid tumor tissues presented high δ65Cu values. These results support the hypothesis that Cu isotopes and plasma trace elements may serve as suitable biomarkers of thyroid cancer diagnosis.

Association between pre-diagnostic dietary copper, zinc, and copper-to-zinc ratio and severity of ovarian cancer

“…The reasons for inconsistency may be the diversity in sample size, study population, especially for study outcomes. On the other hand, our findings of Zn from subgroup analysis are in line with previous studies ( 24 , 26 , 40 , 41 ). For example, two multicenter prospective cohort studies from Europe presented that a higher circulating concentration of Zn was inversely related to the risk of hepatocellular carcinoma and colorectal cancer ( 24 , 40 ).…”

“…Moreover, in the women of BMI < 25 kg/m 2 and comorbidities, high dietary Cu and Zn intake were accompanied by the emergence of well-differentiated OC with a lower severity. These findings were consistent with some studies ( 24 , 26 , 38 , 40 , 41 ) but different from others ( 23 , 39 , 42 , 43 ).…”

“…Up to now, no prior study aimed to explore the association between pre-diagnosis intake of dietary Cu, Zn, and Cu/Zn ratio and the severity of OC. Additionally, epidemiological evidence of other tumors has been limited and inconsistent ( 23 , 24 , 26 , 38 – 43 ). On the one hand, our findings on the Cu and Cu/Zn ratio were consistent with the results from Atakul et al ( 38 ) but contrary to others ( 23 , 39 , 42 , 43 ).…”

“…Furthermore, another cohort proved that higher serum Cu and Cu/Zn ratio might be associated with worse hepatocellular carcinoma survival ( 25 ). Kazi et al ( 26 ) showed that Cu isotopes and plasma trace elements might serve as suitable biomarkers of thyroid cancer diagnosis. Of note, one meta-analysis and Mendelian randomization study showed that lower circulating Zn might be causally associated with higher OC risk, while no causal effect of circulating Cu on OC risk was found ( 27 ).…”

The position of geochemical variables as causal co-factors of diseases of unknown aetiology

“…In children and adults, the normal copper/zinc (Cu/Zn) ratio is about 1:1 (Faber et al [ 330 ]; Bjørklund [ 82 ]). A similar ratio 1.0 ± 0.3 is given for body fluids (e,g., plasma) of healthy adults (Bahi et al [ 331 ]; Kazi Tani et al [ 332 ]).…”